The UMCCC High-Throughput Screening (HTS) Core is a new core which offers center investigators the opportunity to translate hypothesis-driven research into clinically relevant discoveries. In general these efforts focus on dissecting the cellular and molecular mechanisms of cancer through the application of chemical genomics strategies. The UMCCC-HTS Core provides access to compound libraries, screening services, expert consultation, and information sharing for researchers interested in HTS of small molecules, natural product extracts and/or siRNA genomes. The biological and chemical collections at the core are also available for cell profile screening, targeted biology approaches and structure-based molecular modeling. The Core also provides screening to several regional universities and has ongoing collaborations with a number of outside non-profit research Institutions. The core staff assist researchers with assay development, provide training in general HTS techniques, supervise screening campaigns on biomedical targets, manage assay results In a secure relational database and provide advice on counter and secondary screening. Within the HTS Core, medicinal chemistry resources are available for consultation on appropriate follow-up compounds and structure-activity relationship (SAR) analysis. The UMCCC-HTS Core also has an alliance with the Center for Computational Medicine end Bioinformatics (CCMB) to use bioinformatics tools (ConceptGen) for analysis of siRNA HTS results (Sautor et al., 2010). The Core can fully support UMCCC objectives to Identify small molecule probes, potential therapeutic leads and genomic pathways Implicated In malignant diseases, Cancer biology (and relevant genetic models) has been investigated using biochemical and cell-based assays and many of these are amenable to HTS technologies such as flow cytometry, high-content analysis, spectrophotometric detection and transcriptional reporter systems (Collins and Workman, 2006). siRNA HTS, using whole genome or selected subsets of genes, provides pathway analysis and mechanism-based Interrogation of specific genes responsible for human cancer processes. The core and its database of screening results can be used for Individual target-based drug discovery or to Investigate specific chemotypes that affect related targets. Thus, the UMCCC-HTS core is well-positioned to facilitate the discovery of chemical probes for identification and interrogation of cancer targets at the molecular level.